The Pathophysiology of Gastroesophageal Reflux

Part of the Respiratory Medicine book series (RM, volume 2)


Based upon pH monitoring studies, up to 50 reflux episodes a day into the esophagus (below pH 4.0) are considered normal. Exposure to gastric refluxate does not result in the development of disease in the majority of the population, implying that there are intrinsic defense mechanisms that act to maintain mucosal integrity. It is proposed that mucosal inflammation and Barrett’s esophagus occur when reflux is in excess and/or there is a breakdown in the defense mechanisms. The integrity of the human esophageal mucosa depends on several defense mechanisms that protect it against corrosive refluxate. These protective mechanisms can be classified as pre-epithelial (lower esophageal sphincter, peristalsis, and saliva), epithelial (structural defenses, epidermal growth factor, transforming growth factor, Na+/H+ exchanger, carbonic anhydrase, and heat shock proteins), and post-epithelial (blood supply) defenses. In the esophagus, peristalsis and salivary bicarbonate provide for restoration of neutral pH after a reflux episode has occurred. The larynx has no comparable acid clearance mechanism and is therefore much more susceptible to damage by gastric reflux than the esophagus, with three or fewer reflux episodes per week causing laryngeal symptoms and endoscopic findings.

The role of gastric acid in reflux-attributed esophagitis and Barrett’s esophagus is well documented in the literature. It is also widely accepted that extra-esophageal reflux contributes to many other conditions of the aerodigestive tract, including chronic laryngeal inflammation and disease. Recent studies using combined multichannel intraluminal impedance—pH monitoring revealed that the majority of extra-esophageal reflux events are in fact not acidic and that there is often a symptom association with nonacid reflux events. These data highlight a role for the other components of gastric refluxate: bile, trypsin, and pepsin in nonacid reflux. We have shown that pepsin causes laryngeal cell damage independent of the pH of the refluxate and therefore may be responsible for reflux-attributed symptoms refractory to acid suppression therapy and symptoms associated with nonacid reflux events.


Esophagus Gastroesophageal reflux (GERD) Larynx Laryngopharyngeal reflux (LPR) Defense mechanisms Nonacid reflux Acid Pepsin Bile Trypsin 


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© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Department of Otolaryngology and Communication SciencesMedical College of WisconsinMilwaukeeUSA

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